Advances in High Throughput Proteomics Profiling in Establishing Potential Biomarkers for Gastrointestinal Cancer

Abstract

Gastrointestinal cancers (GICs) remain the most diagnosed cancers and accounted for the highest cancer-related death globally. The prognosis and treatment outcomes of many GICs are poor because most of the cases are diagnosed in advanced metastatic stages. This is primarily attributed to the deficiency of effective and reliable early diagnostic biomarkers. The existing biomarkers for GICs diagnosis exhibited inadequate specificity and sensitivity. To improve the early diagnosis of GICs, biomarkers with higher specificity and sensitivity are warranted. Proteomics study and its functional analysis focus on elucidating physiological and biological functions of unknown or annotated proteins and deciphering cellular mechanisms at molecular levels. In addition, quantitative analysis of translational proteomics is a promising approach in enhancing the early identification and proper management of GICs. In this review, we focus on the advances in mass spectrometry along with the quantitative and functional analysis of proteomics data that contributes to the establishment of biomarkers for GICs including, colorectal, gastric, hepatocellular, pancreatic, and esophageal cancer. We also discuss the future challenges in the validation of proteomics-based biomarkers for their translation into clinics.

Keywords: biomarkers; gastrointestinal cancer; mass spectrometry; multi-omics; proteomics.

Figure 1

Types of cancer biomarkers. Biomarkers are mostly found in body fluids including blood, urine, saliva, and also in cancer tissues. Cancer biomarkers belong to a variety of biological elements such as DNA, mRNAs, proteins, long non-coding RNAs (lncRNAs), miRNAs, exosomes, cellular metabolites, and organic materials. This figure was based on a published article by Wu et al. (2015) [9].

Figure 2

A typical workflow of bottom-up mass spectrometry. Proteins are collected from patients or experiments, and then chemically or enzymatically digested for conversion into the mixture of peptides. The peptides are then ready for mass spectrometry instrumentation and separated into a spectrum according to the mass value. Finally, the proteins are analyzed by using database search or computation analysis.